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Despite their structural homology, Notch1 and Notch2 exhibit discrete phenotypic characteristics and functional nuances that necessitate their individualized targeting in specific medical scenarios. Aberrant Notch signaling, often driven by the dysregulated activity of one receptor over the other, is implicated under various pathological conditions. Notch1 dysregulation is frequently associated with T\u2010cell acute lymphoblastic leukemia, whereas Notch2 perturbations are linked to B\u2010cell malignancies and solid tumors, including breast cancer. Hence, tailored therapeutic interventions that selectively inhibit the relevant Notch receptor need to be devised to disrupt the signaling pathways driving the specific disease phenotype. In this review, we emphasize the importance of distinct tissue\u2010specific expression patterns, functional divergence, disease\u2010specific considerations, and the necessity to minimize off\u2010target effects that collectively underscore the significance of \u201cindividualized\u201d targeting for Notch1 and Notch2. This comprehensive review sheds light on the receptor\u2010specific characteristics of Notch1 and Notch2, providing insights into their roles in cellular processes and offering opportunities for developing tailored therapeutic interventions in the fields of biomedical research and clinical practice.<\/jats:p>","DOI":"10.1111\/ejh.14312","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T10:53:38Z","timestamp":1731408818000},"page":"213-230","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Delineating Notch1 and Notch2: Receptor\u2010Specific Significance and Therapeutic Importance of Pinpoint Targeting Strategies for Hematological Malignancies"],"prefix":"10.1111","volume":"114","author":[{"given":"Priyadharshini","family":"Tamizhmani","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Biotechnology and Genetic Engineering Bharathiar University  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